Abstract 4428
Background
Cutaneous melanoma (CM) deserves prominence among tumors due to its high mortality. Single nucleotide variants (SNVs) in genes of immune system pathways in T lymphocytes and abnormal melanocytes may favor tumor proliferation and progression. The aim of the present study was to verify whether SNVs JAK1 c.1648 + 1272G>A and c.991-27C>T and JAK2 c.-1132G>T and c.-139G>A alter the risk of CM and prognosis of CM patients.
Methods
We analysed 248 patients with CM seen at diagnosis at the General Hospital and 274 blood donors (controls) from the Haematology and Haematology Centre of the University of Campinas (UNICAMP). Genotypes of SNVs were identified in DNA of blood samples by real time polimerase chain reaction (RT-PCR), and gene expressions were evaluated by quantitative PCR (qPCR). The statistical meaning of diferences between groups was calculated by t test and Mann-Whitney test. The logistic regression was used to obtain odds ratio (ORs) adjusted for age, cutaneous phototype, nevi and sun exposure, considering the 95% confidence interval (CI). The progression free survival and overall survival were obtained using the Kaplan-Meier estimates and differences between curves were analyzed by the log-rank test. The prognostic value of each variable in patients survival was verified through the univariate and multivariate Cox analyses.
Results
Patients with the JAK1 c.991-27CC genotype (1,22 vs. 0,75 UA, P = 0,01) and allele C (1,11 vs. 0,75 UA, P = 0,02) showed higher mRNA than others. The median follow-up of CM patients was 93 months (variation: 5-221 months). In univariate Cox analysis, patients with the JAK1 c.1648 + 1272GG and JAK1 c.991-27CC isolated genotypes and JAK1 c.1648 + 1272GG plus JAK1 c.991-27CC combined genotype had 1,78, 1,71 and 1,82 more chances of presenting progression of disease, respectively. Patients with JAK1 c.1648 + 1272GG plus JAK1 c.991-27CC plus JAK2 c.-1132GG plus JAK2 c.-139GG combined genotype had 2,11 more chance of presenting disease progression than others.
Conclusions
Our data suggest, for the first time, that JAK1 c.1648 + 1272G>A and c.991-27C>T and JAK2 c.-1132G>T and c.-139G>A SNVs of the JAK/STAT intracellular signaling pathway can alter JAK1 expression and prognosis of CM patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
CAPES, FAPESP.
Disclosure
All authors have declared no conflicts of interest.
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